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(American Journal of Pathology. 2000;157:867-875.)
© 2000 American Society for Investigative Pathology

Regular Articles

Photodynamic Therapy Induces Apoptosis in Intimal Hyperplastic Arteries

Glenn M. LaMuraglia^*, Jan Schiereck^*, Joerg Heckenkamp^*, Giuseppe Nigri^*, Peter Waterman^*, Dariusz Leszczynski and Sylvie Kossodo^*

From the Division of Vascular Surgery^*
and Wellman Laboratories of Photomedicine,
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Photodynamic therapy (PDT) generates free radicals through the absorption of light by photosensitizers. PDT shows promise in the treatment of intimal hyperplasia, which contributes to restenosis, by completely eradicating cells in the vessel wall. This study investigates the mechanisms of PDT-induced cell death. PDT, using the photosensitizer chloroaluminum-sulfonated phthalocyanine (1 mg/kg) and laser light ( = 675 nm) 100 J/cm² was administered to rat carotid arteries after balloon injury-induced intimal hyperplasia. Apoptosis was determined by cell morphology with light microscopy and transmission electron microscopy, DNA cleavage by terminal dUTP nick-end labeling staining, and nucleosomal fragmentation (ladder pattern) by DNA agarose gel electrophoresis. Four hours after PDT, apoptosis was observed in vascular cells, as evidenced by terminal dUTP nick-end labeling staining and transmission electron microscopy. Within 24 hours no cells were present in the neointima and media. Immunofluorescence using an -smooth muscle cell actin antibody confirmed the disappearance of all neointimal and medial cells within 24 hours. No inflammatory cell infiltrate was observed during this time frame. Apoptosis was sharply confined to the PDT treatment field. These data demonstrate that vascular PDT induces apoptosis as a mechanism of rapid, complete, and precise cell eradication in the artery wall. These findings and the lack of inflammatory reaction provide the basis for understanding and developing PDT for a successful clinical application in the treatment of hyperplastic conditions such as restenosis.

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